The true physiological function of "carbonic anhydrase B", the second most abundant protein in red cells, will be sought in a fundamental study of acid-base catalysis and of certain candidate physiological substrates. The relation between the rate of 02 release from red cells following their acidification (Bohr effect), and carbonic anhydrase C function in red cells will be quantified, and the physiological significance of the Bohr effect defined. The electrolyte and acid-base composition of uterine fluid, particularly in relation to progestational and carbonic anhydrase activity, will be measured. The role of this enzyme in the maintenance of early pregnancy will be studied. The remarkable property of cardiac muscle to form HCO3 very rapidly will be explored, in relation to the possible role of carbonic anhydrase in muscle, and to ion shifts in the heart related to function. Inhibition of gastric HCl secretion will be studied with carbonic anhydrase inhibitors more diffusible and more powerful than acetazolamide. Underlying all of these studies is continued work on the kinetics of the reactions CO2 plus H2O reversibly yields H2CO3 and CO2 plus OH- reversibly yields HCO3, particularly at 37 degrees, and the means whereby their catalysis by carbonic anhydrase is inhibited by sulfonamides and anions. Finally, attention will be given to the localization of carbonic anhydrase within tissues, and within cells by new histochemical approaches. The approach is interdisciplanary, and involves a continuum from chemical to physiological aspects of the subject, and a view toward medical utility. Potentially these include problems of pregnancy, thyroid disease, heart disease, and gastric ulcers.